Internal medicine

Neuroscience

Receptor

Sleep onset

Psychiatry

Eye movement

Dopaminergic

Inhibitory postsynaptic potential

Psychology

Non-rapid eye movement sleep

Hypothalamus

Nucleus accumbens

GABAergic

Wakefulness

Glutamatergic

Ventral tegmental area

Lateral hypothalamus

Dopamine

Insomnia

Optogenetics

Electroencephalography

Glutamate receptor

Medicine

Nature Neuroscience

We screened for novel circuits in the mouse brain that promote wakefulness. Chemogenetic activation experiments and electroencephalogram recordings pointed to glutamatergic/nitrergic (NOS1) and GABAergic neurons in the ventral tegmental area (VTA). Activating glutamatergic/NOS1 neurons, which were wake- and rapid eye movement (REM) sleep-active, produced wakefulness through projections to the nucleus accumbens and the lateral hypothalamus. Lesioning the glutamate cells impaired the consolidation of wakefulness. By contrast, activation of GABAergic VTA neurons elicited long-lasting non-rapid-eye-movement-like sleep resembling sedation. Lesioning these neurons produced an increase in wakefulness that persisted for at least 4 months. Surprisingly, these VTA GABAergic neurons were wake- and REM sleep-active. We suggest that GABAergic VTA neurons may limit wakefulness by inhibiting the arousal-promoting VTA glutamatergic and/or dopaminergic neurons and through projections to the lateral hypothalamus. Thus, in addition to its contribution to goal- and reward-directed behaviors, the VTA has a role in regulating sleep and wakefulness. Yu, Li et al. show that VTA GABA and glutamate neurons induce sleep and waking, respectively, via projections to the lateral hypothalamus and nucleus accumbens. Thus, in addition to influencing reward-directed behaviors, the VTA regulates arousal.

GABA and glutamate neurons in the VTA regulate sleep and wakefulness